Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome. The results were used to demonstarte the usefulness of applying HuMiChip to human microbiome studies.
Project description:An alternative to the animal model to address the microbiome-host molecular interactions. We describe the development and applicability of 3D microfluidic devices equipped with a peristaltic-like movement to enhance the robustness and to address the interspecies differences that may reduce the major roadblock to therapeutic implementations.
Project description:HuMiChip was used to analyze human oral and gut microbiomes, showing significantly different functional gene profiles between oral and gut microbiome.
Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.
Project description:The objectives of this study were to establish a microbiome profile for oral epithelial dysplasia using archival lesion swab samples to characterize the community variations and the functional potential of the microbiome using 16S rRNA gene sequencing
Project description:Systemic infection induces conserved physiological responses that include both resistance and ‘tolerance of infection’ mechanisms. Among these responses, temporary anorexia associated with an infection is often beneficial. It poses, however, a problem for the trillions of microbes residing in the gastrointestinal tract, as they also experience reduced substrate availability. We hypothesized that under anorectic conditions caused by infection, the host might activate protective mechanisms to support the gut microbiota during the acute phase of the disease. Here, we report that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α1,2-fucosylation of the small intestine epithelial cells (IEC). The process requires sensing of TLR agonists and production of IL-23 by dendritic cells, activation of innate lymphoid cells and expression of α1,2-Fucosyltransferase-2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is utilized by microbiota, as shown using reporter bacteria and by transcriptional profiling of the gut microbiome. Fucosylation also reduces the expression of bacterial virulence genes within the commensal gut microbiome and improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host’s resources to maintain host-microbial interactions during pathogen-induced stress. RNA-Seq analysis of the murine gut microbiome following LPS exposure. Fut2-/- (B6.129X1-Fut2tm1Sdo/J) mice were backcrossed greater than 7 generations to BALB/c. Fut2-/- (KO) and Fut2+/- (Het) animals were analyzed.
Project description:Background: The microbiome is increasingly being linked to cancer risk. Little is known about the lung and oral cavity microbiomes in healthy smokers (SM), and even less for electronic cigarette (EC) users, compared healthy never-smokers (NS). Methods: In a cross-sectional pilot study of SM (N=8), EC users (N=10) and NS (N=10) saliva and bronchoscopy-collected bronchoalveolar lavage samples were collected. Bacteria species were identified through metatranscriptome profiling by RNA-sequencing to study associations with the lung and oral microbiome. Pairwise comparisons and linear modeling was assessed with false discovery rates <0.1. Results: Total bacterial load was similar for the SM, EC users and NS, and there was no differences in the bacterial diversity across groups. In the lung, there were 44 bacterial species that were statistically significantly different for SM/NS, 80% of which were decreased in the SM. There were 12 bacterial species that were different for SM/EC users, all of which were decreased, 10 of which were also identified in the SM/NS comparison. The 2 bacterial species unique to SM/EC comparison were Neisseria sp. KEM232 and Curvibacter sp. AEP1-3. From the top 5 decreased species in SM/EC, 3 were also identified in the SM/NS comparison (Neisseria elongata, Neisseria sicca, and Haemophilus parainfluenzae) and 2 of these were unique to the SM/EC comparison (Neisseria zoodegmatis and Ottowia sp. oral taxon 894). There were 8 species increased in SM compared to NS, none of which are known to be clinically significant. In the oral microbiome, 152 bacteria species were differentially abundant for the SM/NS analysis, and only 17 for the EC/NS comparison, all which were also present in SM/NS comparisons. There were 21 bacteria that were differentially abundant in both the lung and oral cavity for SM and NS, 95% also were decreased in the SM. Conclusion: Smoking and EC use do not appear to materially affect the lung microbiome, although differences are noted of unclear clinical significance. Most differentially abundant bacteria decreased, which may be due to a toxic effect of cigarette smoke, including a change in humidity or heating. Given the low number of overlapping oral and lung microbes, the oral microbiome does not appear to be a good surrogate for smoking-related effects in the lung.